Summary Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years ...have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy.
Prion Diseases Tee, Boon Lead; Longoria Ibarrola, Erika Mariana; Geschwind, Michael D
Neurologic clinics,
11/2018, Letnik:
36, Številka:
4
Journal Article
Recenzirano
Prions diseases are uniformly fatal neurodegenerative diseases that occur in sporadic, genetic, and acquired forms. Acquired prion diseases, caused by infectious transmission, are least common. Most ...prion diseases are not infectious, but occur spontaneously through misfolding of normal prion proteins or genetic mutations in the prion protein gene. Although most prion diseases are not caused by infection, they can be transmitted accidentally. Certain infection control protocols should be applied when handling central nervous system and other high-risk tissues. New diagnostic methods are improving premortem and earlier diagnosis. Treatment trials have not shown improved survival, but therapies may be available soon.
To test whether different-sized iron oxide-containing Embosphere (IOE) particles can be detected by dedicated magnetic resonance (MR) imaging when injected intraarterially in an animal model of liver ...cancer and whether their distribution could be accurately predicted by MR imaging before confirmation with histopathologic analysis.
Twenty New Zealand White rabbits implanted with VX2 liver tumor were randomly assigned to undergo embolization with 100-300-microm particles (group S; n = 10) or 300-500-microm particles (group L; n = 10). Embolization was performed with the catheter placed in the proper hepatic artery. T2*-weighted multiplanar MR imaging was performed within 24 hours after the procedure to detect paramagnetic IOE susceptibility artifact. MR imaging interpretation parameters included presence of artifact in the artery and/or at the tumor bed. Hematoxylin and eosin- and Prussian blue-stained pathologic slides were also obtained and the presence of IOE was evaluated similarly.
The MR detectability rates for IOEs were 100% in both groups. Paramagnetic susceptibility IOE artifact inside the tumor was detected in 30% of group S animals. On pathologic analysis, IOE particles were detected inside the tumor in 70% of this group. IOEs in group L were found outside the tumor within the hepatic artery on MR imaging and histopathologic study (P < .05).
MR imaging readily detected IOE particles in an animal model of liver cancer regardless of the particle size. The smaller particles (100-300 microm) were delivered inside the tumor or in close proximity to the tumor margin, justifying their use for drug delivery or precise embolization.
The field of interventional oncology includes tumor ablation as well as the use of transcatheter therapies such as embolization, chemoembolization, and radioembolization. Terminology and reporting ...standards for tumor ablation have been developed. The development of standardization of terminology and reporting criteria for transcatheter therapies should provide a similar framework to facilitate the clearest communication among investigators and provide the greatest flexibility in comparing established and emerging technologies. An appropriate vehicle for reporting the various aspects of catheter directed therapy is outlined, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings. Methods for standardizing the reporting of outcomes toxicities, complications, and other important aspects that require attention when reporting clinical results are addressed. It is the intention of the group that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication for reporting the various aspects of transcatheter management of hepatic malignancy that will translate to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes.
Rapidly progressive dementia Geschwind, Michael D; Haman, Aissa; Miller, Bruce L
Neurologic clinics,
08/2007, Letnik:
25, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Rapidly progressive dementias (RPDs) are neurologic conditions that develop subacutely over weeks to months or, rarely, acutely over days. In contrast to most dementing conditions that take years to ...progress to death, RPD quickly can be fatal. It is critical to evaluate patients who have RPD without delay, usually in a hospital setting, as they may have a treatable condition. This review discusses a differential diagnostic approach to RPD, emphasizing neurodegenerative, toxic and metabolic, infectious, autoimmune, neoplastic, and other conditions to consider.
A potent new adenosine triphosphate inhibitor--3-bromopyruvate (3-BrPA)--has been shown to have antitumor effects when injected intraarterially in the hepatic artery of rabbits with VX-2 tumors. The ...authors performed a stepwise study in rabbits to determine the therapeutic dose and method of delivery of 3-BrPA.
White New Zealand rabbits with VX-2 tumors were used for this study. Eight animals were examined to establish the maximum tolerated dose (2.5 or 5.0 mmol/L of 25-mL 3-BrPA) as a single bolus injection. The 2.5 mmol/L dose was then used to compare three methods of delivery: injection of one bolus, two 12.5-mL serial bolus injections administered 1 hour apart, and continuous infusion of 25 mL for 1 hour. Finally, dose-response analysis was performed by using 10 groups of three animals each, with 1-hour intraarterial infusions of 3-BrPA (25 mL) at incremental doses of 0.25 mmol/L (range, 0.5-2.5 mmol/L) with phosphate buffered saline used for control animals. All animals were sacrificed at 48 hours, and histopathologic analysis was performed. chi2 statistics were used to analyze the data.
The maximum tolerated dose of 3-BrPA was 2.5 mmol/L; however, it caused substantial peripheral liver necrosis. These effects were minimized when 3-BrPA was infused over 1 hour. Complete tumor necrosis was identified in all samples with at least 2.0 mmol/L of 3-BrPA. The 1.75 mmol/L concentration was identified as therapeutic because it caused complete tumor apoptosis and minimal toxicity (P < .001).
The results identified both the therapeutic dose (1.75 mmol/L) and the method of infusion (1 hour intraarterial infusion) of 3-BrPA. This potent new treatment may prove to be an effective way of treating liver cancer and may become part of a new class of anticancer drugs based on the inhibition of tumor metabolism.
Abstract Background Leucine-rich glioma inactivated 1 (LGI1) is a component of the voltage-gated potassium channel complex. IgG antibodies against LGI1 are associated with immunotherapy-responsive ...encephalitis and epilepsies. LGI1-antibody concentrations are 10–100 times greater in serum than in cerebrospinal fluid (CSF). Oligoclonal IgG bands are rarely found in patients with LGI1-antibody encephalitis or epilepsy. These observations raise questions about the sources of the B cells that result in production of LGI1 antibodies and how the IgGs reach the brain. We aimed to investigate the migration and expansions of peripheral and central B cells to the production of LGI1-specific IgG. Methods We performed PCR amplification and next generation deep immune repertoire sequencing of immunoglobulin (Ig) heavy chain variable regions (VH) from CSF and subsorted peripheral blood B-cell populations from two patients with limbic encephalitis and faciobrachial dystonic seizures associated with LGI1 antibodies. Bioinformatics clustering of related IgM-VH or IgG-VH transcripts was used to determine whether active B-cell diversification could be observed, and whether intrathecal B-cell repertoires, if present, were related to peripheral B cells. Findings We identified clusters of related Ig-VH transcripts in the CSF of both patients. Within these clusters there was a range of somatic hypermutations along the IGHV germline segment-derived portion. In addition, we identified a large number of closely related Ig-VH clusters that were common to both CSF and peripheral blood, including a small number of dominating Ig-VH clusters that might represent the most active clonally related B-cell populations. Interpretation Our data suggest that some B-cell affinity maturation occurs inside the CNS compartment in LGI1-antibody encephalitis. Somatic hypermutation rates point to a CSF antigen-driven activation of clonally related B cells that shape the intrathecal immune repertoire. The target antigen or antigens of these clonally related B cells remain unknown; our work continues to determine the relative contribution of intrathecally activated and peripheral LGI1-specific B cells in this autoimmune CNS disease. Funding Wellcome Trust Intermediate Fellowship to SRI, Fulbright-MS Society, Epilepsy Research UK, BMA Vera Down Research Grant.
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